Our general hypothesis is that age-related decreases in skeletal muscle perfusion diminish the stimulus for anabolism in elderly muscle. Our preliminary results suggest that following a bolus ingestion of amino acids, elderly muscle protein synthesis is markedly delayed as compared to young. We hypothesize that in response to an increase in blood amino acid concentration, changes in interstitial fluid concentrations and muscle protein synthesis occur more sluggishly in the elderly. Further, we propose that these sluggish responses in elderly occur at least in part because of decreased muscle perfusion. We further hypothesize that exercise-induced increases in muscle blood flow, in the presence of amino acids, has an interactive effect on young and elderly skeletal muscle inducing an amplified anabolic response. The goal of this proposal is to determine the effects of increased muscle perfusion on muscle protein synthesis in elderly, either through aerobic exercise or peripheral vasodilation (femoral arterial infusion of sodium nitroprusside at 8 microg/min) both with and without amino acids. Further, we intend to utilize a novel 4-pool model of amino acid kinetics which allows for the determination of blood, intracellular and interstitial fluid amino acid concentrations. Moreover, we intend to use a novel contrast enhanced ultrasound technique to measure total leg blood flow (i.e. laser Doppler flowmetry) and microvascular perfusion (i.e. capillary flow and volume) in skeletal muscle. Muscle kinetics will be evaluated in response to a continuous infusion of amino acids under basal and increased blood flow conditions, in response to a bolus ingestion of amino acids under basal and increased blood flow conditions, and in response to 45 minutes of moderate aerobic exercise (45 min at 40 percent of VO2max), both with and without amino acid supplementation. Results from these studies will provide evidence as to the regulatory role of increased muscle perfusion, amino acid supplementation and aerobic exercise as means of improving skeletal muscle protein synthesis in the elderly.